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CHICAGO—Use of calcium-channel blockers, alpha-blockers or angiotensin-converting enzyme (ACE) inhibitors appears to offer no advantages in improving clinical outcomes compared with use of diuretics when treating hypertension among individuals with metabolic syndrome, according to a report in the January 28 issue of Archives of Internal Medicine, one of the JAMA/Archives journals. This appears particularly true for black patients.

Patients with hypertension (high blood pressure) and metabolic syndrome are at high risk for the complications of cardiovascular disease, according to background information in the article. The metabolic syndrome was defined as hypertension plus at least two of the following factors: diabetes or pre-diabetes; a body mass index (BMI) of at least 30; high triglyceride levels; or low levels of high-density lipoprotein (“good” cholesterol). Because some medications for high blood pressure (including alpha-blockers, ace inhibitors and calcium channel blockers) have a favorable metabolic profile—for instance, have more favorable short-term effects on blood glucose or blood cholesterol levels—they have been advocated over other drugs (beta-blockers and diuretics) for the treatment of patients with metabolic syndrome.

Jackson T. Wright Jr., M.D., Ph.D., of Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, and colleagues analyzed data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). A total of 42,418 participants with hypertension and at least one other risk factor for cardiovascular disease were randomly assigned to take a diuretic (chlorthalidone, 15,255 patients), a calcium channel blocker (amlodipine besylate, 9,048 patients), an alpha-blocker (doxazosin mesylate, 9,061 patients) or an ACE inhibitor (lisinopril, 9,054 patients). Each drug was used to start treatment and other drugs could be added if necessary to control blood pressure. Patients were followed for an average of 4.9 years for all drugs except the alpha-blocker; that arm of the trial was discontinued after an average 3.2 years of follow-up in light of increased rates of cardiovascular disease, including a near two-fold increased rates of heart failure, when compared with the diuretic arm. A total of 23,077 ALLHAT participants (54.4 percent) met criteria for metabolic syndrome.

“No differences were noted among the four treatment groups, regardless of race or metabolic syndrome status for the primary end point (non-fatal myocardial infarction [heart attack] and fatal coronaryheart disease),” the authors write. Among patients with the metabolic syndrome (7,327 black and 15,750 white patients), the calcium channel blocker, ACE inhibitor and alpha-blocker had higher rates of heart failure compared with the diuretic; the ACE inhibitor and the alpha-blocker also had an increased risk of combined cardiovascular disease.

“The lack of benefit of the agents with the most favorable metabolic profile (i.e., ACE inhibitors and alpha-blockers) was especially marked in the black participants with metabolic syndrome,” the authors write. “The magnitude of the excess risk of end-stage renal [kidney] disease (70 percent), heart failure (49 percent) and stroke (37 percent) and the increased risk of combined cardiovascular disease and combined coronary heart disease strongly argue against the preference of ACE inhibitors over diuretics as the initial therapy in black patients with metabolic syndrome. Similar higher risk was noted for those randomized to the alpha-blocker vs. the diuretic.”

“These findings fail to provide support for the selection of alpha-blockers, ACE inhibitors, or calcium channel blockers over thiazide-type diuretics to prevent cardiovascular or renal outcomes in patients with metabolic syndrome, despite their more favorable metabolic profiles,” the authors conclude.
(Arch Intern Med. 2008;168[2]:207-217).

Editor's Note: This study was supported by a contract from the National Heart, Lung, and Blood Institute and by Pfizer Inc. (ALLHAT). Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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